The development of periodontal disease in adults is believed to be associated with the localized secretion of proteinases from the organism Porphyromonas qingivalis into the dento-gingival cavity. These enzymes can degrade a host of important proteins which include not only those involved in connective tissue structure (e.g., collagen) but also regulato factors such as components, proteinase inhibitors, and bactericidal proteins. Since it is likely that the presence of P. gingivalis causes the recruitment of neutrophils to the dento-gingival cavity and the release of phagocytic proteinases which augment abnormal connective tissue turn-over, the inactivation of regulatory proteins becomes even more important. In order to study the potential dual role of P. gingivalis proteinases more closely, the specific aims of this project are dedicated to 1) their isolation and characterization, 2) determination of their specificity, particularly with regard to the hydrolysis of synthetic substrates and naturally occurring proteins, 3) evaluation of their ability to degrade both inflammatory and anti-inflammatory proteins, and 4) measurement of the effect of naturally occurring proteinase inhibitors (mammalian and bacteria derived) as potential regulators. The long term goals of this proposal are to evaluate the contribution of P. gingivalis proteinases to the development of periodontal disease, determine the structure of these enzymes, and produce inhibitors which can regulate their activity in vivo.